中药新药临床试验中安慰剂模拟效果评价与思考
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摘要
目的探讨中药新药临床试验中安慰剂的模拟效果评价方法和盲法的实施问题,为提高中药双盲临床试验的研究质量提供方法学参考。方法以一个中药新药安慰剂的制作为实例,从形、色、味、气几个方面,通过进行试验药物的可能性判断和安慰剂与试验药的相似性判断,评价中药安慰剂的模拟效果,并分析中药临床试验盲法实施中存在的实际问题。结果评价者对于两种药物是否是试验药物的可能性判断无统计学差异(P>0.05);对于安慰剂与试验药的相似性,两药在外观的评分差异无统计学意义(P>0.05),其一致性达到100%,但安慰剂在颜色、气味、口味上与试验药比较差异均有统计学意义(P<0.05),其一致性分别为50%、10%和15%。结论中药安慰剂在色、气、味上有时很难与试验药完全一致,因此,在试验实施过程中要加强受试者和研究者的依从性管理,减少破盲;在试验结束后评估破盲对试验结果的影响。
Objectives To discuss the methodology of evaluation of traditional Chinese medicine(TCM)placebo simulation effects and the problems of blind implementation and so as to improve the quality of double-blind clinical trials of TCM.Methods Focusing on case of placebo preparation of TCM investigational new drug,simulation effects of the placebo were evaluated in terms of shape,color,taste and smell.The possibility of placebo be a drug and the similarity between placebo and drug were tested.Results There was no significant difference between placebo and investigational new drug to be judged as a drug(P>0.05).As for the similarity between placebo and drug,there was no significantly difference of the shape(P>0.05),for which the similarity was 100%.The color,taste and smell were significant different between placebo and drug(P<0.05),for which the similarity were 50%,10% and 15% respectively.Conclusions It is very difficult to simulate TCM based on its certain color,taste or smell.Therefore,the subjects and the investigators’compliance should be kept to avoid breaking the blind intentionally in the process of the trial and the influence of unblinding should be estimated at the end of the trial.
Objectives To discuss the methodology of evaluation of traditional Chinese medicine(TCM)placebo simulation effects and the problems of blind implementation and so as to improve the quality of double-blind clinical trials of TCM.Methods Focusing on case of placebo preparation of TCM investigational new drug,simulation effects of the placebo were evaluated in terms of shape,color,taste and smell.The possibility of placebo be a drug and the similarity between placebo and drug were tested.Results There was no significant difference between placebo and investigational new drug to be judged as a drug(P>0.05).As for the similarity between placebo and drug,there was no significantly difference of the shape(P>0.05),for which the similarity was 100%.The color,taste and smell were significant different between placebo and drug(P<0.05),for which the similarity were 50%,10% and 15% respectively.Conclusions It is very difficult to simulate TCM based on its certain color,taste or smell.Therefore,the subjects and the investigators’compliance should be kept to avoid breaking the blind intentionally in the process of the trial and the influence of unblinding should be estimated at the end of the trial.
引文
1国家食品药品监督管理总局.《药物临床试验质量管理规范》(局令第3号).Available at:http://www.sda.gov.cn/WS01/CL0288/24473.html.
2国家食品药品监督管理总局.关于征求《药物临床试验质量管理规范》修订稿意见的通知.Available at:http://www.sda.gov.cn/WS01/CL0778/113991.html.
3蒋兆健,刘洁瑜,葛发欢,等.安慰剂在中药新药临床试验研究中的应用及思考.中国现代中药,2013,15(6):463-466.
4国家食品药品监督管理总局药品审评中心.中药新药临床研究一般原则.Available at:http://www.sda.gov.cn/WS01/CL0087/134581.html.
5周跃华,朱家谷.浅谈中药新药临床及药学研究用样品的质量控制.中国中医药信息杂志,2009,16(12):4-5.
6张德翠,段俊国,罗涛.浅谈中药临床试验安慰剂制作中应注意的问题.中药药理与临床,2009,25(2):124-125.
7王琼,王怡茹,齐晓凤,等.随机对照研究中的中药汤剂的安慰剂.世界中医药,2016,11(8):1631-1634.
8刘建平.循证中医药临床研究方法学.北京:人民卫生出版社,2006:121-123.
9唐旭东,卞立群,高蕊,等.中药临床试验安慰剂制作探讨.中国中西医结合杂志,2009,29(7):656-658.
10林媚,唐旭东,王凤云.肠安Ⅰ号及低浓度试验药物对照安慰剂的试验药效学研究.深圳中西医结合杂志,2009,19(5):273-278.
11Brinkhaus B,Pach D,Lüdtke R,et al.Who controls the placebo?Introducing a placebo quality checklist for pharmacological trials.Contemp Clin Trials,2008,29(2):149-156.
12王云飞,阮新民,吴焕林,等.大型双盲临床试验中药安慰剂制备方法及效果评价研究.中药新药与临床药理,2011,22(3):255-258.
13金冠钦,孙黎,夏玲红.中药制剂肾八味胶囊的安慰剂制备及评价研究.中国药师,2014,17(5):734-736.
14王雪峰,董丹,刘芳,等.中药临床试验研究安慰剂制作初探.辽宁中医杂志,2003,30(12):966.
15李秋爽,曹毅,季聪华,等.中药安慰剂质量评价思考.中华中医药杂志(原中国医药学报),2017,32(6):2365-2368.
16王茹茹,刘玉杰,杨添钧,等.中药安慰剂评价客观量化的思考.世界科学技术-中医药现代化,2014,16(3):485-489.
17王燕霞,谢一辉,龚嘉华,等.电子舌在食品药品中的应用.江西中医药大学学报,2014,26(2):79-82.
18韩玉.电子鼻在苍术质量评价中的应用研究.北京:北京中医药大学,2011.
19吴萍,张建武.中药新药临床试验用药品的闭环管理模式研究.中国中药杂志,2013,38(17):2898-2900.
20吴飞,王优杰,洪燕龙,等.中药安慰剂制备和临床使用的研究进展.中国新药杂志,2012,21(18):2161-2164.
2国家食品药品监督管理总局.关于征求《药物临床试验质量管理规范》修订稿意见的通知.Available at:http://www.sda.gov.cn/WS01/CL0778/113991.html.
3蒋兆健,刘洁瑜,葛发欢,等.安慰剂在中药新药临床试验研究中的应用及思考.中国现代中药,2013,15(6):463-466.
4国家食品药品监督管理总局药品审评中心.中药新药临床研究一般原则.Available at:http://www.sda.gov.cn/WS01/CL0087/134581.html.
5周跃华,朱家谷.浅谈中药新药临床及药学研究用样品的质量控制.中国中医药信息杂志,2009,16(12):4-5.
6张德翠,段俊国,罗涛.浅谈中药临床试验安慰剂制作中应注意的问题.中药药理与临床,2009,25(2):124-125.
7王琼,王怡茹,齐晓凤,等.随机对照研究中的中药汤剂的安慰剂.世界中医药,2016,11(8):1631-1634.
8刘建平.循证中医药临床研究方法学.北京:人民卫生出版社,2006:121-123.
9唐旭东,卞立群,高蕊,等.中药临床试验安慰剂制作探讨.中国中西医结合杂志,2009,29(7):656-658.
10林媚,唐旭东,王凤云.肠安Ⅰ号及低浓度试验药物对照安慰剂的试验药效学研究.深圳中西医结合杂志,2009,19(5):273-278.
11Brinkhaus B,Pach D,Lüdtke R,et al.Who controls the placebo?Introducing a placebo quality checklist for pharmacological trials.Contemp Clin Trials,2008,29(2):149-156.
12王云飞,阮新民,吴焕林,等.大型双盲临床试验中药安慰剂制备方法及效果评价研究.中药新药与临床药理,2011,22(3):255-258.
13金冠钦,孙黎,夏玲红.中药制剂肾八味胶囊的安慰剂制备及评价研究.中国药师,2014,17(5):734-736.
14王雪峰,董丹,刘芳,等.中药临床试验研究安慰剂制作初探.辽宁中医杂志,2003,30(12):966.
15李秋爽,曹毅,季聪华,等.中药安慰剂质量评价思考.中华中医药杂志(原中国医药学报),2017,32(6):2365-2368.
16王茹茹,刘玉杰,杨添钧,等.中药安慰剂评价客观量化的思考.世界科学技术-中医药现代化,2014,16(3):485-489.
17王燕霞,谢一辉,龚嘉华,等.电子舌在食品药品中的应用.江西中医药大学学报,2014,26(2):79-82.
18韩玉.电子鼻在苍术质量评价中的应用研究.北京:北京中医药大学,2011.
19吴萍,张建武.中药新药临床试验用药品的闭环管理模式研究.中国中药杂志,2013,38(17):2898-2900.
20吴飞,王优杰,洪燕龙,等.中药安慰剂制备和临床使用的研究进展.中国新药杂志,2012,21(18):2161-2164.